M.Sc Thesis

M.Sc StudentKadry Wisam
SubjectSimulation of Metabolic Pathways
DepartmentDepartment of Computer Science
Supervisor PROF. Ron Pinter


The rapidly increasing number of revealed biological pathways calls for the development and use of simulation methods and tools. Using computer simulations researchers would facilitate their biological analysis and understanding of biological pathways. In this work we deeply explore, examine and compare two biosimulation methods, the Stochastic (Chemical)-p-Calculus and the Hybrid Functional Petri Nets, as they apply to metabolic pathways. By employing appropriate ways of modeling metabolic reactions, we introduce a real-world simulation model of the Reduced Folates Metabolism, the pathway of nucleic acids precursors synthesis, which is essential for DNA synthesis and cellular proliferation and therefore, it plays an important role in cancer and cancer chemotherapy. Using our real world reliable simulation model we perform several virtual experiments that involve three different novel anticancer and chemotherapy drugs. Using these experiments we determine for each drug its signature, i.e. for each drug we determine its ways of inhibiting the cancer and more important, in which quantities. Moreover, we theoretically investigate the steady state phenomena of special structured metabolic pathways under some relaxed conditions on the reactions’ rates using the Stochastic (Chemical)-p-Calculus and the Hybrid Functional Petri Nets simulation methods. Such a theoretical approach gives us a better insight into the convergence capabilities of the two simulation methods and the used simulation algorithms and their asymptotic behavior. Mathematical proofs of the simulations’ algorithms convergence and their steady state solutions which are also illustrated by computer simulations are presented.